A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease.

Proceedings of the National Academy of Sciences of the United States of America
Gürol TuncmanGökhan S Hotamisligil

Abstract

Obesity and the associated pathologies including dyslipidemia, insulin resistance, type 2 diabetes, and cardiovascular disease constitute a major threat to global human health. Yet, the genetic factors that differentially predispose individuals to this cluster of pathologies are unclear. The fatty acid-binding protein aP2 is a cytoplasmic lipid chaperon expressed in adipocytes and macrophages. Mice with aP2 deficiency are partially resistant to obesity-induced insulin resistance and type 2 diabetes, have lower circulating triglycerides, and exhibit marked protection against atherosclerosis. Here, we demonstrate a functionally significant genetic variation at the aP2 locus in humans that results in decreased adipose tissue aP2 expression due to alteration of the CAAT box/enhancer-binding protein binding and reduced transcriptional activity of the aP2 promoter. In population genetic studies with 7,899 participants, individuals that carry this T-87C polymorphism had lower serum triglyceride levels and significantly reduced risk for coronary heart disease and type 2 diabetes compared with subjects homozygous for the WT allele. Taken together, our results indicate that reduction in aP2 activity in humans generate a metabolically fav...Continue Reading

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Citations

Sep 3, 2010·Wiener medizinische Wochenschrift·Carmen GelsingerChristoph F Ebenbichler
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